Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV001171760 | SCV001334604 | likely pathogenic | not provided | 2020-02-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000004074 | SCV002265141 | pathogenic | PHGDH deficiency | 2024-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 135 of the PHGDH protein (p.Arg135Trp). This variant is present in population databases (rs267606949, gnomAD 0.006%). This missense change has been observed in individual(s) with PHGDH-related conditions (PMID: 19235232, 22886422, 26610677). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 3870). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PHGDH protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001171760 | SCV005080566 | likely pathogenic | not provided | 2023-06-15 | criteria provided, single submitter | clinical testing | Reported previously in two unrelated patients with congenital microcephaly, seizures, and severely reduced L-serine in CSF, who also harbored a second variant in PHGDH, phase unknown (PMID: 19235232, 26610677); Published functional studies demonstrate a damaging effect and show that this variant decreases PHGDH enzyme activity (PMID: 19235232, 33753166); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24836451, 33753166, 19235232, 19963421, 26610677, 32594192, 27959531) |
| Fulgent Genetics, |
RCV000675113 | SCV005646557 | likely pathogenic | PHGDH deficiency; Neu-Laxova syndrome 1 | 2024-05-15 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000004074 | SCV000024240 | pathogenic | PHGDH deficiency | 2009-05-01 | no assertion criteria provided | literature only | |
| Counsyl | RCV000675113 | SCV000800664 | uncertain significance | PHGDH deficiency; Neu-Laxova syndrome 1 | 2018-02-21 | flagged submission | clinical testing |